Thrombotic complications are a major cause of death in the industrialized world. Examples of these complications include acute myocardial infarction, unstable angina, chronic stable angina, transient ischemic attacks, strokes, peripheral vascular disease, preeclampsia/eclampsia, deep venous thrombosis, embolism, disseminated intravascular coagulation and thrombotic cytopenic purpura. Thrombotic and restenotic complications also occur following invasive procedures, e.g., angioplasty, carotid endarterectomy, post CABG (coronary artery bypass graft) surgery, vascular graft surgery, stent placements and insertion of endovascular devices and prostheses. It is generally thought that platelet aggregates play a critical role in these events. Blood platelets, which normally circulate freely in the vasculature, become activated and aggregate to form a thrombus with disturbed blood flow caused by ruptured atherosclerotic lesions or by invasive treatments such as angioplasty, resulting in vascular occlusion. Platelet activation can be initiated by a variety of agents, e.g., exposed subendothelial matrix molecules, such as collagen, or by thrombus, which is formed in the coagulation cascade.
MRP-14 is part of the 5100 family comprised of small proteins (˜9-14 kDa) containing two Ca2+-binding EF hand domains. It was first identified as an acute myocardial infarction (MI) gene using transcriptional profiling of platelets from patients with acute coronary syndromes (ACS). When secreted by myeloid cells, it is predominantly found as an MRP-8/14 heterodimer in humans Studies with MRP-14−/− mice determined that MRP-8/14 broadly regulates vascular inflammation and promotes leukocyte recruitment in models of atherosclerosis, restenosis, and vasculitis. More recently, MRP-14 was identified as a highly expressed mediator of thrombosis found on platelets whose knockdown does not affect hemostasis. While MRP-14 deficiency is protective of thrombosis, it had no effect on hemostatic parameters such as tail bleeding time, coagulation, thrombin generation, or platelet adhesion and spreading.